Emergent Concepts of Receptor Pharmacology

Pharmacology, the chemical control of physiology, emerged as an offshoot of physiology when the physiologists using chemicals to probe physiological systems became more interested in the probes than the systems. Pharmacologists were always, and in many ways still are, bound to study drugs in systems they do not fully understand. Under these circumstances, null methods were the main ways in which conclusions about biologically active molecules were made. However, as understanding of the basic mechanisms of cellular function and biochemical systems were elucidated, so too did the understanding of how drugs affected these systems. Over the past 20 years, new ideas have emerged in the field that have completely changed and revitalized it; these are described herein. It will be seen how null methods in isolated tissues gave way to, first biochemical radioligand binding studies, and then to a wide array of functional assay technologies that can measure the effects of molecules on drug targets. In addition, the introduction of molecular dynamics, the appreciation of the allosteric nature of receptors, protein X-ray crystal structures, genetic manipulations in the form of knock-out and knock-in systems and Designer Receptors Exclusively Activated by Designer Drugs have revolutionized pharmacology.